Experimental Drug LOXO-101 Shrinks Tumors with NTRK Fusions

The drug LOXO-101 reduces the size of tumors with NTRK gene fusions, according to an ongoing multicenter phase I trial (No. 2014-1056) led by The University of Texas MD Anderson Cancer Center.

The trial’s goal was to find the highest tolerable dose of LOXO-101 that could be given to patients with advanced solid tumors. LOXO-101 is a selective pan-TRK inhibitor, and this is the first trial using it in humans.

Genomic testing revealed that six of the 41 patients enrolled in the trial had NTRK1 or NTRK3 gene fusions in tumors representing many types of cancer, including sarcoma, gastrointestinal stromal tumor, non–small cell lung cancer, papillary thyroid cancer, and mammary analog secretory carcinoma of the salivary gland.

Tumors in five of the six patients with NTRK fusions demonstrated partial responses to LOXO-101 according to Response Evaluation Criteria in Solid Tumors, and the sixth patient achieved a 21% tumor regression. All six patients continue to receive LOXO-101 and are into at least their seventh 28-day cycle of LOXO-101 without disease progression.

Thus far, LOXO-101 has been well tolerated at various once-daily and twice-daily doses. Common side effects have included fatigue, dizziness, and nausea. The highest tolerable dose for LOXO-101 has not been determined. Data from the phase I trial, which were presented at the American Association for Cancer Research’s annual meeting in April, suggest that LOXO-101 is well tolerated and capable of inducing durable disease control in patients who have tumors with NTRK fusions.

Even as the phase I trial of LOXO-101 continues to enroll patients, a phase II trial (No. 2015-0728), which includes only patients whose tumors test positive for NTRK gene fusions, is under way. Patients in the phase II trial receive 100 mg of LOXO-101 twice daily.

“We are currently enrolling patients with all solid tumor types with NTRK fusions for a phase II trial,” said David Hong, M.D., an associate professor in the Department of Investigational Cancer Therapeutics. “NTRK fusions have been found in nearly every tumor type. The phase II trial is important for generating additional data about LOXO-101 in patients with NTRK fusion cancer, but we also anticipate it will further broaden the range of tumor types that we’ve tested thus far.”